Red blood cell transfusion is associated with increased hemolysis and an acute phase response in a subset of critically ill children.
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ABSTRACT:
SUBMITTER: L'Acqua C
PROVIDER: S-EPMC4831067 | biostudies-literature | 2015 Oct
REPOSITORIES: biostudies-literature
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Red blood cell transfusion is associated with increased hemolysis and an acute phase response in a subset of critically ill children.
L'Acqua Camilla C Bandyopadhyay Sheila S Francis Richard O RO McMahon Donald J DJ Nellis Marianne M Sheth Sujit S Kernie Steven G SG Brittenham Gary M GM Spitalnik Steven L SL Hod Eldad A EA
American journal of hematology 20151001 10
In healthy adults, transfusion of older stored red blood cells (RBCs) produces extravascular hemolysis and circulating non-transferrin-bound iron. In a prospective, observational study of critically ill children, we examined the effect of RBC storage duration on the extent of hemolysis by comparing laboratory measurements obtained before, and 4 hr after, RBC transfusion (N = 100) or saline/albumin infusion (N = 20). Transfusion of RBCs stored for longer than 4 weeks significantly increased plasm ...[more]
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Project description:IntroductionRed blood cell (RBC) transfusion is associated with poor clinical outcome in critically ill patients. We investigated the predictive value of biomarkers on intensive care units (ICU) admission for RBC transfusion within 28 days.MethodsCritically ill patients (n = 175) who admitted to our ICU with organ dysfunction and an expected stay of ≥ 48 hours, without hemorrhage, were prospectively studied (derivation cohort, n = 121; validation cohort, n = 54). Serum levels of 12 biomarkers (hemoglobin, creatinine, albumin, interleukin-6 [IL-6], erythropoietin, Fe, total iron binding capacity [TIBC], transferrin, ferritin, transferrin saturation, folate, and vitamin B12) were measured upon ICU admission, days 7, 14, 21 and 28.ResultsAmong the 12 biomarkers measured upon ICU admission, levels of hemoglobin, albumin, IL-6, TIBC, transferrin and ferritin were statistically different between transfusion and non-transfusion group. Of 6 biomarkers, TIBC upon ICU admission had the highest area under the curve value (0.835 [95% confidence interval] = 0.765-0.906) for predicting RBC transfusion (cut-off value = 234.5 μg/dL; sensitivity = 0.906, specificity = 0.632). This result was confirmed in validation cohort, whose sensitivity and specificity were 0.888 and 0.694, respectively. Measurement of these biomarkers every seven days revealed that albumin, TIBC and transferrin were statistically different between groups throughout hospitalization until 28 days. In validation cohort, patients in the transfusion group had significantly higher serum hepcidin levels than those in the non-transfusion group (P = 0.004). In addition, joint analysis across derivation and validation cohorts revealed that the serum IL-6 levels were higher in the transfusion group (P = 0.0014).ConclusionDecreased TIBC upon ICU admission has high predictive value for RBC transfusion unrelated to hemorrhage within 28 days.
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Project description:BackgroundTransfusion of blood at the limits of approved storage time is associated with lower red blood cell (RBC) post-transfusion recovery and hemolysis, which increases plasma cell-free hemoglobin and iron, proposed to induce endothelial dysfunction and impair host defense. There is noted variability among donors in the intrinsic rate of storage changes and RBC post-transfusion recovery, yet genetic determinants that modulate this process are unclear.MethodsWe explore RBC storage stability and post-transfusion recovery in murine models of allogeneic and xenogeneic transfusion using blood from humanized transgenic sickle cell hemizygous mice (Hbatm1PazHbbtm1TowTg(HBA-HBBs)41Paz/J) and human donors with a common genetic mutation sickle cell trait (HbAS).FindingsHuman and transgenic HbAS RBCs demonstrate accelerated storage time-dependent hemolysis and reduced post-transfusion recovery in mice. The rapid post-transfusion clearance of stored HbAS RBC is unrelated to macrophage-mediated uptake or intravascular hemolysis, but by enhanced sequestration in the spleen, kidney and liver. HbAS RBCs are intrinsically different from HbAA RBCs, with reduced membrane deformability as cells age in cold storage, leading to accelerated clearance of transfused HbAS RBCs by entrapment in organ microcirculation.InterpretationThe common genetic variant HbAS enhances RBC storage dysfunction and raises provocative questions about the use of HbAS RBCs at the limits of approved storage.
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Project description:Rationale: In critically ill patients, a hemoglobin transfusion threshold of <7.0 g/dl compared with <10.0 g/dl improves organ dysfunction. However, it is unclear if transfusion at a hemoglobin of <7.0 g/dl is superior to no transfusion. Objectives: To compare degrees of organ dysfunction between transfusion and no transfusion at a hemoglobin threshold of <7.0 g/dl among critically ill patients using quasiexperimental regression discontinuity methods. Methods: We performed regression discontinuity analysis using hemoglobin measurements from patients admitted to intensive care units in three cohorts (Medical Information Mart for Intensive Care IV, eICU, and Premier Inc.), estimating the change in organ dysfunction (modified sequential organ failure assessment score) in the 24- to 72-hour window following each hemoglobin measurement. We compared hemoglobin concentrations just above and below 7.0 g/dl using a "fuzzy" discontinuity approach, based on the concept that measurement noise pseudorandomizes similar hemoglobin concentrations on either side of the transfusion threshold. Results: A total of 11,181, 13,664, and 167,142 patients were included in the Medical Information Mart for Intensive Care IV (MIMIC-IV), eICU, and Premier Inc. cohorts, respectively. Patient characteristics below the threshold did not differ from those above the threshold, except that crossing below the threshold resulted in a >20% absolute increase in transfusion rates in all three cohorts. Transfusion was associated with increases in hemoglobin concentration in the subsequent 24-72 hours (MIMIC-IV, 2.4 [95% confidence interval (CI), 1.1 to 3.6] g/dl; eICU, 0.7 [95% CI, 0.3 to 1.2] g/dl; Premier Inc., 1.9 [95% CI, 1.5 to 2.2] g/dl) but not with improvement in organ dysfunction (MIMIC-IV, 4.6 [95% CI, -1.2 to 10] points; eICU, 4.4 [95% CI, 0.9 to 7.8] points; Premier Inc., 1.1 [95% CI, -0.2 to 2.3] points) compared with no transfusion. Conclusions: Transfusion was not associated with improved organ dysfunction compared with no transfusion at a hemoglobin threshold of 7.0 g/dl, suggesting that evaluation of transfusion targets other than a hemoglobin threshold of 7.0 g/dl may be warranted.
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Project description:BACKGROUND:Some countries have limited the maximum allowable storage duration for red cells to 5 weeks before transfusion. In the US, red blood cells can be stored for up to 6 weeks, but randomized trials have not assessed the effects of this final week of storage on clinical outcomes. METHODS:Sixty healthy adult volunteers were randomized to a single standard, autologous, leukoreduced, packed red cell transfusion after 1, 2, 3, 4, 5, or 6 weeks of storage (n = 10 per group). 51-Chromium posttransfusion red cell recovery studies were performed and laboratory parameters measured before and at defined times after transfusion. RESULTS:Extravascular hemolysis after transfusion progressively increased with increasing storage time (P < 0.001 for linear trend in the AUC of serum indirect bilirubin and iron levels). Longer storage duration was associated with decreasing posttransfusion red cell recovery (P = 0.002), decreasing elevations in hematocrit (P = 0.02), and increasing serum ferritin (P < 0.0001). After 6 weeks of refrigerated storage, transfusion was followed by increases in AUC for serum iron (P < 0.01), transferrin saturation (P < 0.001), and nontransferrin-bound iron (P < 0.001) as compared with transfusion after 1 to 5 weeks of storage. CONCLUSIONS:After 6 weeks of refrigerated storage, transfusion of autologous red cells to healthy human volunteers increased extravascular hemolysis, saturated serum transferrin, and produced circulating nontransferrin-bound iron. These outcomes, associated with increased risks of harm, provide evidence that the maximal allowable red cell storage duration should be reduced to the minimum sustainable by the blood supply, with 35 days as an attainable goal.REGISTRATION. ClinicalTrials.gov NCT02087514. FUNDING:NIH grant HL115557 and UL1 TR000040.
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